排序方式: 共有70条查询结果,搜索用时 15 毫秒
41.
L Strekowski O Zegrocka M Henary M Say M J Mokrosz B M Kotecka L Manzel D E Macfarlane 《Bioorganic & medicinal chemistry letters》1999,9(13):1819-1824
On the basis of a systematic SAR analysis of substituted quinolines, a derivative 32 was synthesized that shows half-maximal inhibition of the immunostimulatory effect of CpG-oligodeoxynucleotides in vitro at the concentration of 0.24 nM. 相似文献
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Strekowski L Henary M Kim N Michniak BB 《Bioorganic & medicinal chemistry letters》1999,9(7):1033-1034
N-Aroyl-, N-Arylsulfonyl-, and N-Aryl-S,S-dimethyliminosulfuranes have been synthesized and evaluated as potential dermal penetration enhancers. The title compound and Azone exhibit similar activities for permeation of hydrocortisone through hairless mouse skin. 相似文献
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The 3D jury system has predicted the methyltransferase fold for the nsp13 protein of the SARS coronavirus. Based on the conservation of a characteristic tetrad of residues, the mRNA cap-1 methyltransferase function has been assigned to this protein, which has potential implications for antiviral therapy. 相似文献
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Andriy A MokhirJolanta ?wi?tek-Kozlowska Elena G PetkovaIgor O Fritsky Lucjan JerzykiewiczAnatoliy A Kapshuk TatianaYu Sliva 《Inorganica chimica acta》2002,329(1):113-121
Complex formation properties of a novel water soluble thiazolyloxime 2-(4-methylthiazol-2-yl)-2-(hydroxyimino)acetic acid (H3L1) with Cu2+ and Ni2+ were investigated in solution by potentiometrical and spectral (UV-Vis, EPR, NMR) methods. All Cu2+ and most of Ni2+ complex species detected in solution were found to have square-planar MN4 core with oxime and heterocyclic nitrogen atoms which was rationalized in terms of destabilizing effect of repulsive interaction between oxygen atom of carboxylic group and nitrogen atom of thiazole ring in N,O-coordinated ligand conformation. It has been found that stability of metal complexes in a series of oxime ligands is dependent upon basicity of nitrogen atom of oxime group. The thiazolyloxime forms less stable complexes with Cu2+ but stronger ones with Ni2+ ions when compared to parent 2-(hydroxyimino)propanoic acid. The lower stability obtained for Cu2+ complexes was elucidated in terms of negative inductive effect of the thiazole and nitrile substituents as well as an effect of intramolecular attractive interaction between thiazolyl sulfur and oxime oxygen atoms in thiazolyloxime. In the case of Ni2+ the complexes formed are square-planar and it is why thiazolyl ligand is more effective in metal ion binding than simple 2-(hydroxyimino)propanoic acid forming only octahedral species. The solid state structure of the Co3+ complex K3[Co(HL1)3]·5.5H2O (1) was studied by X-ray analysis. The thiazolyloxime ligand is coordinated to Co3+ via oxime nitrogen and carboxylate oxygen atoms forming five-membered chelate rings. 相似文献
45.
Non-covalent drug/DNA interactions are difficult to study and because of this, the significance of such interactions from a safety standpoint and their contribution to positive genetic toxicology test findings is poorly understood. It is shown in the present study that such interactions may be detected and quantified in Chinese hamster V79 cells by an adaptation of the bleomycin amplification assay. This assay measures the ability of a test compound to enhance the DNA damaging activity of the antibiotic bleomycin using micronucleus formation as an endpoint. Results are presented examining the bleomycin amplification activity of known intercalating agents, groove-binding agents and other structurally diverse classes of compounds for which intercalative status has not been reported. The assay reveals a strong and predictable SAR for amplification activity based on number and orientation of aromatic rings. Moreover, excellent correlations are observed between DNA binding (viscometric analyses) and DNA amplification in V79 cells for a series of seven experimental compounds. The assay is shown to be useful in understanding the genotoxicity of marketed antihistamines and to help explain genetic toxicology findings observed in a series of novel pharmaceutical entities. It is proposed that assessment of bleomycin amplification activity of novel compounds in early genotoxicity prescreening may provide important information upon which to base synthesis of compounds with minimal or no genotoxic liability. 相似文献
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Pawlikowska-Pawlęga B Misiak LE Zarzyka B Paduch R Gawron A Gruszecki WI 《Biochimica et biophysica acta》2012,1818(7):1785-1793
The effect of genistein on the liposomes formed with dipalmitoylphosphatidylcholine was studied with the application of Fourier-transform infrared spectroscopy, nuclear magnetic resonance ((1)H NMR) and electron paramagnetic resonance techniques. Membranous structures organization of human skin fibroblasts and colon myofibroblasts was also examined using fluorescence and electron microscopy. The strongest rigidifying effect of genistein with respect to polar head groups was concluded on the basis of the effect of the flavonoid on the shape of NMR lines attributed to -N(+)(CH(3))(3) groups. The rigidifying effect of genistein with respect to the hydrophobic core of lipid membranes was also concluded from the genistein-dependent broadening of the NMR lines assigned to -CH(2) groups and terminal -CH(3) groups of alkyl chains. EPR data supported ordering effect of genistein of the hydrophobic core in the liquid-crystalline phase (L(α)). The analysis of the FTIR spectra of the two-component liposomes showed that genistein incorporates into DPPC membranes via hydrogen bonding between the lipid polar head groups in the C-O-P-O-C segment and its hydroxyl groups. Both fluorescence microscopy and ultrastructural observation revealed changes in membranous structures organization as aftermath of genistein treatment. In conclusion, genistein localized within membranes changes the properties of membrane that can be followed by the changes inside cells being crucial for pharmacological activity of genistein used in cancer or other disease treatment. 相似文献
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Puntervoll P Linding R Gemünd C Chabanis-Davidson S Mattingsdal M Cameron S Martin DM Ausiello G Brannetti B Costantini A Ferrè F Maselli V Via A Cesareni G Diella F Superti-Furga G Wyrwicz L Ramu C McGuigan C Gudavalli R Letunic I Bork P Rychlewski L Küster B Helmer-Citterich M Hunter WN Aasland R Gibson TJ 《Nucleic acids research》2003,31(13):3625-3630
Multidomain proteins predominate in eukaryotic proteomes. Individual functions assigned to different sequence segments combine to create a complex function for the whole protein. While on-line resources are available for revealing globular domains in sequences, there has hitherto been no comprehensive collection of small functional sites/motifs comparable to the globular domain resources, yet these are as important for the function of multidomain proteins. Short linear peptide motifs are used for cell compartment targeting, protein-protein interaction, regulation by phosphorylation, acetylation, glycosylation and a host of other post-translational modifications. ELM, the Eukaryotic Linear Motif server at http://elm.eu.org/, is a new bioinformatics resource for investigating candidate short non-globular functional motifs in eukaryotic proteins, aiming to fill the void in bioinformatics tools. Sequence comparisons with short motifs are difficult to evaluate because the usual significance assessments are inappropriate. Therefore the server is implemented with several logical filters to eliminate false positives. Current filters are for cell compartment, globular domain clash and taxonomic range. In favourable cases, the filters can reduce the number of retained matches by an order of magnitude or more. 相似文献
50.
Strekowski L Hojjat M Wolinska E Parker AN Paliakov E Gorecki T Tanious FA Wilson WD 《Bioorganic & medicinal chemistry letters》2005,15(4):1097-1100
Several substituted quinolin-4-amines and heteroaromatic analogs were synthesized and evaluated for interaction with triplex polydA.2polydT and duplex polydA.polydT by using UV-thermal melting experiments. Excellent triple-helix DNA ligands with high affinity toward T.A.T triplets and triple/duplex selectivity were designed through a rational approach. 相似文献